Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary addition to the burgeoning field of immunotherapy. CAR T-cells are engineered by combining a T-cell receptor with the antigen-binding site of an immunoglobulin that allows the hybrid cell to target antigens of interest. CAR T-cell therapy has been approved to treat various hematologic malignancies, including relapsed or refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. While the treatment efficacy is exciting, challenges remain in understanding the unique spectrum of adverse effects of CAR T-cell therapy, including cytokine release syndrome and neurotoxicity. Innovative research is underway to expand this therapy into solid tumors and fields beyond hematology and oncology. To date, there has been limited research into ophthalmic uses and considerations of CAR T-cell therapy. This review focuses on preclinical investigations into CAR T-cell therapy for retinoblastoma and uveal melanoma, as well as ophthalmic complications of CAR T-cell therapy.
Discovery and characterization of serologic biomarkers has revolutionized the diagnostic framework of systemic and paraneoplastic autoimmune neuro-ophthalmic diseases. Expanding recognition of the multiple ocular and visual manifestations of these conditions highlights the important role of the referring provider in identifying potential cases. Increasing ease of access to serologic testing also enables these practitioners to initiate the diagnostic work-up in suspected cases. We aimed to provide an update on the current knowledge surrounding and use of relevant autoimmune biomarkers by correlating specific clinical neuro-ophthalmic manifestations with autoantibody biomarkers. The utility of select biomarkers for myasthenia gravis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein-IgG-associated disorder, opsoclonus-myoclonus syndrome, anti-collapsin-response mediator protein-5 optic neuropathy, and glial fibrillary acidic protein-IgG-associated disease are discussed with particular focus on the clinical contexts in which to consider testing.
OBJECTIVE: We describe the Baltimore Reading and Eye Disease Study, report baseline ocular findings, and explore the feasibility of eye examinations in the school setting. DESIGN: Prospective, school-based cohort study. PARTICIPANTS: Students in second and third grades. METHODS: Baseline eye examinations, including near and distance presenting visual acuity (VA), stereopsis, ocular alignment, dilated retinal examination, and cycloplegic refraction, were performed in 12 Baltimore public schools during the 2014-15 school year. MAIN OUTCOME MEASURES: Presenting VA, prevalence of refractive error, and other ocular findings. RESULTS: Among the 1054 eligible students, 321 participated. There were 271 (84.4%) African American and 186 (57.9%) female students; mean age was 7.9 ± 0.8 years. Cycloplegia was achieved in 308. The mean presenting distance and near VA was 0.1 ± 0.2 logMAR (range -0.1 to 1.5) and 0.1 ± 0.2 logMAR (range 0.0-1.6) in the better-seeing eye, respectively. The most common ocular findings were +1.00 diopter (D) or greater hyperopia (34.7%), -0.50 D or greater myopia (29.5%), 1.00 D or greater astigmatism (23.4%), and convergence insufficiency (7.2%). Thirty-seven (11.5%) children needed referral to an eye care provider; 10% of students required glasses full-time. CONCLUSIONS: Whereas the majority of second and third grade students in this study have good VA and minimal refractive error, 1 in 9 have an ocular finding necessitating further evaluation. It was feasible to conduct cycloplegic eye examinations in the school setting.
PURPOSE: People with central vision loss (CVL) watch television, videos and movies, but often report difficulty and have reduced video comprehension. An approach to assist viewing videos is electronic magnification of the video itself, such as Bubble Magnification. METHODS: We created a Bubble Magnification technique that displayed a magnified segment around the centre of interest (COI) as determined by the gaze of participants with normal vision. The 15 participants with CVL viewed video clips shown with 2× and 3× Bubble Magnification, and unedited. We measured video comprehension and gaze coherence. RESULTS: Video comprehension was significantly worse with both 2× (p = 0.01) and 3× Bubble Magnification (p < 0.001) than the unedited video. There was no difference in gaze coherence across conditions (p ≥ 0.58). This was unexpected because we expected a benefit in both video comprehension and gaze coherence. This initial attempt to implement the Bubble Magnification method had flaws that probably reduced its effectiveness. CONCLUSIONS: In the future, we propose alternative implementations of Bubble Magnification, such as variable magnification and bubble size. This study is a first step in the development of an intelligent-magnification approach to providing a vision rehabilitation aid to assist people with CVL.
PURPOSE: To evaluate the clinical effect of topical cyclosporine A (CsA) (0.05%) on dry eye patients with Sjogren's syndrome (SS) and non-Sjogren's syndrome (NSS). METHOD: This retrospective comparative study includes the dry eye (DE) patients who were treated with topical CsA. DE patients were divided into two groups as follows: DE with Sjogren's syndrome (DE-SS) and DE with Non-Sjogren's syndrome (DE-NSS). Dry eye parameters were recorded at baseline and each visit. RESULTS: Schirmer's test 1 scores were 2.7 ± 0.5 mm at baseline and 3.5 ± 0.7 mm at 12th month in DE-SS, 2.9 ± 0.7 mm at baseline and 9.5 ± 0.7 mm in DE-NSS groups at 12th month. Mean ST score was higher in DE-NSS group than DE-SS group at sixth and 12th months of the treatment (both p = 0.001). Tear break-up time score showed a significant improvement in DE-NSS group, and it was lower in DE-NSS group than DE-SS group group at sixth and 12th months of the treatment (p = 0.044 and 0.027, respectively). Mean OSDI score was lower in DE-NSS group than DE-SS group at sixth and 12th months of the treatment (p = 0.030 and 0.032, respectively). CONCLUSION: Topical CsA seems to be more effective in the treatment of the DE-NSS.
AIMS: To compare widefield swept-source optical coherence tomography angiography (WF SS-OCTA) with ultra-widefield colour fundus photography (UWF CFP) and fluorescein angiography (UWF FA) for detecting diabetic retinopathy (DR) lesions. METHODS: This prospective, observational study was conducted at Massachusetts Eye and Ear from December 2018 to October 2019. Proliferative DR, non-proliferative DR and diabetic patients with no DR were included. All patients were imaged with a WF SS-OCTA using a Montage 15×15 mm scan. UWF CFP and UWF FA were taken by a 200°, single capture retinal imaging system. Images were independently evaluated for the presence or absence of DR lesions including microaneurysms (MAs), intraretinal microvascular abnormalities (IRMAs), neovascularisation elsewhere (NVE), neovascularisation of the optic disc (NVD) and non-perfusion areas (NPAs). All statistical analyses were performed using SPSS V.25.0. RESULTS: One hundred and fifty-two eyes of 101 participants were included in the study. When compared with UWF CFP, WF SS-OCTA was found to be superior in detecting IRMAs (p<0.001) and NVE/NVD (p=0.007). The detection rates of MAs, IRMAs, NVE/NVD and NPAs in WF SS-OCTA were comparable with UWF FA images (p>0.05). Furthermore, when we compared WF SS-OCTA plus UWF CFP with UWF FA, the detection rates of MAs, IRMAs, NVE/NVD and NPAs were identical (p>0.005). Agreement (κ=0.916) between OCTA and FA in classifying DR was excellent. CONCLUSION: WF SS-OCTA is useful for identification of DR lesions. WF SS-OCTA plus UWF CFP may offer a less invasive alternative to FA for DR diagnosis.
Ophthalmology has been at the forefront of medical specialties adopting artificial intelligence. This is primarily due to the "image-centric" nature of the field. Thanks to the abundance of patients' OCT scans, analysis of OCT imaging has greatly benefited from artificial intelligence to expand patient screening and facilitate clinical decision-making.In this review, we define the concepts of artificial intelligence, machine learning, and deep learning and how different artificial intelligence algorithms have been applied in OCT image analysis for disease screening, diagnosis, management, and prognosis.Finally, we address some of the challenges and limitations that might affect the incorporation of artificial intelligence in ophthalmology. These limitations mainly revolve around the quality and accuracy of datasets used in the algorithms and their generalizability, false negatives, and the cultural challenges around the adoption of the technology.
PURPOSE: To describe 3 cases of corneal clearance after the use of topical rho-kinase inhibitor, netarsudil, in the setting of endothelial cell dysfunction in comparison to one case without corneal clearance after the use of netarsudil. METHODS: Four patients presenting to a busy academic clinical corneal practice with visual complaints from corneal edema secondary to endothelial cell dysfunction were treated with topical netarsudil one drop daily in the affected eye. RESULTS: Corneal clearance was observed in 1) a case of peripheral corneal edema in the setting of iridocorneal endothelial syndrome after 4 weeks on netarsudil, 2) a case of corneal edema in the setting of early penetrating keratoplasty graft failure after 2-week use of netarsudil, and 3) a case of corneal edema in the setting of chronic penetrating keratoplasty graft failure after 4-week use of netarsudil. Corneal clearance was not observed in a case of corneal edema in the setting of pseudophakic bullous keratopathy from previous complicated intraocular lens exchange surgery with placement of an anterior chamber intraocular lens after the use of netarsudil for 12 weeks. CONCLUSIONS: Addition of topical rho-kinase inhibitor in the form of netarsudil can result in corneal clearance in a variety of certain cases of endothelial cell dysfunction, not previously documented in the literature.
In this review we discuss the broad clinical application of qAF and provide a descriptive summary of the phenotypic findings of different chorioretinal pathologies. Quantitative Fundus autofluorescence (qAF) is a novel developing technology that can aid in diagnosis and longitudinal disease monitoring by measuring and comparing autofluorescence intensities. Fundus autofluorescence (FAF) is a noninvasive imaging method that creates a density map of the fluorophores of the ocular fundus and provides both functional and topographic anatomic information about retinal cells. Fluorophores are molecules that have the ability to temporarily absorb irradiated light, and emit a small amount of light of a different wavelength. Different endogenous fluorophores can be found in the ocular fundus. Changes in accumulation of retinal fluorophores usually indicate retinal pathology and create characteristic patterns of hyper-autofluorescence and hypo-autofluorescence that help establish a diagnosis. qAF allows a safe non-invasive visualization of the retina, enables a standard for AF intensities comparison and aids to the understanding of the genotype-phenotype correlations.
The cornea actively maintains its own avascular status to preserve its ultimate optical function. This corneal avascular state is also defined as "corneal angiogenic privilege", which results from a critical and sensitive balance between anti-angiogenic and pro-angiogenic mechanisms. In our review, we aim to explore the complex equilibrium among multiple mediators which prevents neovascularization in the resting cornea, as well as to unveil the evolutive process which leads to corneal angiogenesis in response to different injuries.
Neurotrophic Keratitis (NK) is a degenerative disorder of the cornea characterized by decreased or absent sensory corneal innervation, corneal epitheliopathy and impaired healing.The clinical presentation of NK can range from persistent epithelial defects to corneal perforation and management is often both challenging and protracted. Historically, the management of NK has consisted of non-specific strategies to facilitate corneal epithelial healing such as lubrication, bandage contact lenses and tarsorrhaphy. Recent advances in the development of therapeutics for NK have provided new and efficacious targeted strategies for its management.In this article, we review recombinant human nerve growth factor (Cenegermin), currently approved for clinical use in the United States and Europe, as well as other promising therapeutic options that are in pre-clinical development such as thymosine β4, connexin43 inhibitors, and artificial extracellular matrix components.
Douglas VP, Douglas KA, Reinshagen KL, Chwalisz BK. Case 292. Radiology 2021;299(1):234-236.Abstract
History A 24-year-old right-handed woman presented to a neuro-ophthalmology clinic in Massachusetts in the summer with acute binocular diplopia when looking down and to the left, which started about 1 month earlier. Her medical history was notable for Raynaud syndrome, recurrent streptococcal pharyngitis, and an allergy to amoxicillin. Three days prior to developing diplopia, she presented to an outside emergency department due to fever, chills, and back pain. She received ciprofloxacin for presumed urinary tract infection based on urinalysis, which demonstrated few bacteria and was negative for leukocyte esterase, nitrites, and white blood cells. She then presented again to an outside emergency department for diplopia evaluation. Initial MRI and MR angiography of the brain at that time did not demonstrate any relevant findings, and the patient was referred to our department for neuro-ophthalmic evaluation, where she was seen 4 weeks later. Neuro-ophthalmic examination revealed 20/20 visual acuity in both eyes, and a right hypertropia in left gaze, downgaze and right head tilt, with right eye excyclotorsion. There were no ocular signs of myasthenia gravis or thyroid eye disease, nor did the patient report ocular or systemic symptoms. She denied recent travel. High-spatial-resolution MRI of the brain and orbit were performed (Figs 1, 2).
ABSTRACT: A 44-year-old woman presented with 2 painful and self-limited episodes of binocular horizontal diplopia within 1 year that at the beginning were thought to be secondary to microvascular insult. Her medical history was significant for Cushing syndrome status post transsphenoidal resection with bilateral adrenalectomy 4 years prior, hypertension, and diabetes mellitus. Neuro-ophthalmic evaluation was significant for left abduction deficit and incomitant esotropia consistent with left abducens nerve palsy. Of note, the patient had experienced a similar episode but on the contralateral side a few months prior. Although initially MRI of the brain demonstrated stable residual postoperative finding in the sella, upon review, an heterogenous T-1 hypointense marrow in the clivus was noted. Hypermetabolism of the clivus was also noted on computed tomography positron emission tomography of the skull base. A clival biopsy demonstrated a corticotroph adenoma with elevated proliferation index and scattered mitoses. A corticotroph pituitary adenoma after adrenalectomy, also known as Nelson syndrome, was diagnosed. Radiation therapy was offered to the patient, and resolution of symptoms was gradually observed.
PURPOSE: To define and quantify patterns of objectively measured daily physical activity by level of visual field (VF) damage in glaucoma patients including: (1) activity fragmentation, a metric of health and physiologic decline, and (2) diurnal patterns of activity, a measure of rest and activity rhythms. DESIGN: Prospective cohort study. PARTICIPANTS: Older adults diagnosed with glaucoma or suspected glaucoma. METHODS: Degree of VF damage was defined by the average VF sensitivity within the integrated VF (IVF). Each participant wore a hip accelerometer for 1 week to measure daily minute-by-minute activity for 7 consecutive days. Activity fragmentation was calculated as the reciprocal of the average activity bout duration in minutes, with higher fragmentation indicating more transient, rather than sustained, activity. Multivariate linear regression was used to test for cross-sectional associations between VF damage and activity fragmentation. Multivariate linear mixed-effects models were used to assess the associations between VF damage and accumulation of activity across 6 3-hour intervals from 5 am to 11 pm. MAIN OUTCOME MEASURES: Activity fragmentation and amount of activity (steps) over the course of the day. RESULTS: Each 5-dB decrement in IVF sensitivity was associated with 16.3 fewer active minutes/day (P < 0.05) and 2% higher activity fragmentation (P < 0.05), but not with the number of active bouts per day (P = 0.30). In time-of-day analyses, lower IVF sensitivity was associated with fewer steps over the 11 am to 2 pm, 2 pm to 5 pm, and 5 pm to 8 pm periods (106.6, 93.1, and 89.2 fewer steps, respectively; P < 0.05 for all), but not over other periods. The activity midpoint (the time at which half of the daily activity is completed) did not vary across level of VF damage. CONCLUSIONS: At worse levels of VF damage, glaucoma patients demonstrate shorter, more fragmented bouts of physical activity throughout the day and lower activity levels during typical waking hours, reflecting low physiologic functioning. Further work is needed to establish the temporality of this association and whether glaucoma patients with such activity patterns are at a greater risk of adverse health outcomes associated with activity fragmentation.
BACKGROUND: Older adults with visual impairments experience a higher risk of falling, and are more vulnerable to adverse health consequences associated with falls than those with normal vision. This study characterizes longitudinal changes in objectively measured physical activity and fear of falling (FoF) occurring after various types of falls in visually impaired older adults. DESIGN: Prospective cohort study. SETTING: Hospital-based enrollment. PARTICIPANTS: People with glaucoma or suspected glaucoma. MEASUREMENTS: Falls were defined as unintentionally coming to rest on the ground or a lower level, and injurious falls were determined though follow-up calls. Study participants were categorized into three groups-fallers with injurious consequences, fallers without injurious consequences, and non-fallers based on fall status in the first year. Physical activity was assessed by waist-bound accelerometer. FoF was evaluated by questionnaire, with Rasch modeling generating FoF scores where higher scores reflected worse FoF. The 3-year longitudinal changes of physical activity and FoF were modeled using mixed-effects models. RESULTS: In linear models fully adjusted for visual field damage and other covariates, physical activity among injurious fallers showed greater annual (per year) declines in daily steps (-425 steps/d, 95% confidence interval (CI) = -793, -57), daily active minutes (-13 min/d, 95% CI = -21, -6), and daily moderate and vigorous physical activity (MVPA) minutes (-3 MVPA minutes/d, 95% CI = -5, 0) over the 3-year period as compared to non-fallers; however, physical activity did not significantly decline among non-injurious fallers. No longitudinal increases in FoF scores were observed in injurious or non-injurious fallers when compared to non-fallers. CONCLUSION: Among visually impaired older adults, injurious falls identified prospectively over 12 months contributed to a significant decline in physical activity over a 3-year period, while minimal changes were observed in FoF.